Purpose: The purpose of this protocol is to compare the genetic and epigenetic effects between diesel exhaust and ozone exposure in healthy individuals and in mild/moderate asthmatics.

Participants: The investigators will recruit up to 30 mild to moderate asthmatics and up to 50 healthy adults to participate in this study.

Procedures (methods): Subjects will be exposed to clean air, to 300 µg/m3 of diesel exhaust for 2 hours and to 0.3 ppm of ozone for 2 hours with intermittent exercise in a controlled environment chamber. Primary endpoints will include spirometry and lung cell changes post-exposure. Secondary endpoints will include analysis of blood clotting/coagulation factors, Holter monitoring of cardiac parameters, analysis of soluble factors present in plasma and bronchial lavage and analysis of intracellular factors present in lung tissue obtained from a brush biopsy.

Analysis of soluble factors present in plasma and bronchial lavage and analysis of intracellular factors present in lung tissue obtained from a brush biopsy following exposure to clean air ozone or diesel exhaust

Exposure to clean air will be conducted in an exposure chamber at the EPA Human Studies Facility on the UNC campus. Each subject will be exposed to clean air for 2 hours. Subjects will begin exercising on an exercise bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 25 L/m2/BSA followed by a 15 minute rest period. The exposure atmosphere will be at approximately 40 + 10% RH and approximately 22 + 2 oC.

Other: Clean Air

Exposure to air which has been scrubbed to remove air pollutants including ozone and particles.

Other Name: CA

Ozone exposure

Exposure to 0.3ppm ozone will be conducted in an exposure chamber at the EPA Human Studies Facility on the UNC campus. Each subject will be exposed for 2 hours. Subjects will begin exercising on an exercise bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 25 L/m2/BSA followed by a 15 minute rest period. The exposure atmosphere will be at approximately 40 + 10% RH and approximately 22 + 2 oC. Ozone exposures will be conducted in a (6 ft x 6 ft x 8 ft) stainless steel chamber with a continuous supply of exposure medium. Ozone will be monitored continuously.

Other: Ozone exposure

Exposure to 0.3ppm ozone for 2 hours

Other Name: O3

Diesel exhaust exposure

Exposure to diesel exhaust will be conducted in an exposure chamber at the EPA Human Studies Facility on the UNC campus. Each subject will be exposed to diesel exhaust (up to 300 ug/m3). Subjects will begin exercising on an exercise bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 25 L/m2/BSA followed by a 15 minute rest period. The exposure atmosphere will be at approximately 40 + 10% RH and approximately 22 + 2 oC. The DE will be generated from a diesel generator used to power a load bank that is located outside the Human Studies Facility, and subsequently introduced into the exposure chamber after different dilutions with clean HEPA and charcoal filtered and humidified air to give a chamber concentration of up to 300 μg/m3.

Other: Diesel exhaust

Diesel exhaust generated from a diesel generator delivered to the exposure at a target concentration of 300 μg/m3

Other Names:

DE

DEP

18Ozone

Exposure to ozone generated using the heavy non-radioactive isotope of oxygen (18O). Exposure to 0.3ppm 18O will be conducted in an exposure chamber at the EPA Human Studies Facility on the UNC campus. Each subject will be exposed for 2 hours. Subjects will begin exercising on an exercise bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 25 L/m2/BSA followed by a 15 minute rest period. The exposure atmosphere will be at approximately 40 + 10% RH and approximately 22 + 2 oC. Ozone exposures will be conducted in a (6 ft x 6 ft x 8 ft) stainless steel chamber with a continuous supply of exposure medium. Ozone will be monitored continuously.

Other: Ozone18

Exposure to ozone generated using the heavy non-radioactive isotope of oxygen (18O).

If the subject is pregnant, attempting to become pregnant or breastfeeding.

Allergy to any medications which may be used or prescribed in the course of this study.

Subjects currently taking mega doses of vitamins and supplements, homeopathic/naturopathic medicines or medications which may impact the results of the PM and/or ozone challenge or interfere with any other medications potentially used in the study (to include systemic steroids and beta blockers). Subjects must refrain from all over the counter anti-inflammatory agents including those for allergies, and naproxen, and anti-oxidants for a period of one week prior to exposure. Medications not specifically mentioned here may be reviewed by the investigators prior to a subject's inclusion in the study.

Smoking history within 2 years of the study.

Use of inhaled steroids, cromolyn, or leukotriene inhibitors (Montelukast, Zafirkulast, etc) initiated within the past month (except for use of cromolyn exclusively prior to exercise). Patients must be on a stable regimen of therapy.

Untreated hypertension (> 150 systolic, > 90 diastolic)

Dementia.

Unspecified illnesses, which in the judgment of the investigator might increase the risk associated with PM inhalation challenge or exercise, will be a basis for exclusion.

History of skin allergy to tape or electrodes.

Subjects who do not understand or speak English

Subjects who are unable to perform moderate exercise

Exclusion criteria for bronchoscopy:

Any food or fluids after midnight prior to bronchoscopy

FEV1/FVC ratio less than 60% predicted on AM of bronchoscopy.

Regular use of aspirin or other nonsteroidal anti-inflammatory drugs (which inhibit platelet function).

5. If the subject is pregnant, attempting to become pregnant or breastfeeding. 6. Allergy to any medications which may be used or prescribed in the course of this study 7. Subjects currently taking mega doses of vitamins and supplements, homeopathic/naturopathic medicines or medications which may impact the results of the PM challenge or interfere with any other medications potentially used in the study (to include systemic steroids and beta blockers). Subjects must refrain from all over the counter anti-inflammatory agents including those for allergies, and naproxen, and anti-oxidants for a period of one week prior to exposure. Medications not specifically mentioned here may be reviewed by the investigators prior to a subject's inclusion in the study.

8. Dosing level of an inhaled steroid must be consistent with mild asthma as outlined by the NHLBI NAEPP guidelines. Regular use of oral corticosteroids, or use of inhaled steroid at doses typically used for severe asthma, will result in exclusion of that individual from the protocol.

9. Severe asthmatics as defined by: nighttime symptoms of cough or wheeze greater than 1 time per week at baseline, daily exacerbation of asthma or requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness, but not to include prophylactic use of albuterol prior to exercise), more than mild interference with normal activity, any episode of physician directed emergency treatment for asthma requiring oral corticosteroid therapy within the past twelve months.

10. Smoking history within 2 years of study. 11. Use of inhaled steroids, cromolyn, or leukotriene inhibitors (Montelukast, Zafirkulast, etc) initiated within the past month (except for use of cromolyn exclusively prior to exercise). Patients must be on a stable regimen of therapy.

12. History of skin allergy to tape or electrodes. 13. History of respiratory diseases other than allergic rhinitis and asthma 14. Untreated hypertension (> 150 systolic, > 90 diastolic) 15. Dementia. 16. Unspecified illnesses, which in the judgment of the investigator might increase the risk associated with PM inhalation challenge or exercise, will be a basis for exclusion.

17. Subjects who do not understand or speak English 18. Subjects who are unable to perform moderate exercise

Exclusion criteria for bronchoscopy:

Any food or fluids after midnight prior to bronchoscopy

FEV1/FVC ratio less than 60% predicted on AM of bronchoscopy.

Regular use of aspirin or other nonsteroidal anti-inflammatory drugs (which inhibit platelet function).

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01492517